Table 1.

Chemically dependent biomolecular pathways changed by some polyphenolic compounds, as a complement to Fig. 2

Name of the polyphenolic compound	Anti-oncogenic mechanisms of action in skin cancer
Curcumin	Inhibition of p-4EBP1 [48, 49] Decreases 12-O-tetradecanoylphorbol-13-acetate-induced protein kinase C translocation and inhibits IGF-1- carcinogenic signaling [48–53] Decreasing of UVB-induced thymine dimer-positive cells, expression of PCNA, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells [54] Inhibition of PGE-2, NO, and COX-2 NF-κB [54–56] Inhibition of ROS production and toxic membrane UVA-induced damage [56] Stimulates cytotoxic T-lymphocyte response downregulating myeloid-derived suppressor cells, regulatory T cells, and IL-6 and chemokine ligand-2 [65] Increases TNF-α, IFN-γ, and CD8+ T-cell population [65, 66]
Ellagic acid	Promotion of G1 cell cycle arrest, increasing of apoptosis and decreasing of IL-1β, IL-6, IL-8, IL-10, and NF-κβ [94, 100, 101] Reduction of MCP-1, and TNF-α [101] Expression of ICAM-1-UVB-dependent [100] Expression of superoxide dismutase and heme-oxygenase 1 [105] Inhibition of apoptosis: prevention of DNA fragmentation and decreasing of both mitrochondria impairment and endoplasmatic reticulum stress [105]
Epicatechin gallate	Suppression of UVA-mediated release of labile iron [117] Suppression of cyclin D1 [121] Induction of caspase-3 activity [121, 122] Inhibition of ribonuclease-A by copper complexes [123]
Honokiol	Induces cycle G0/G1 cell arrest [157] Inhibition of ROS-dependent NF-κB [158] Decreasing of ATP pool [153] Decreasing of Notch signaling [154, 156] Inhibition on the UVB-induced expression of COX-2, PGE2, proliferating cell nuclear antigen, and some pro-inflammatory cytokines [137] Inhibition of Ki-67 expression and an increase in TUNEL-positive cells [160]
Resveratrol	Stimulates Nrf2 [181–184] Produces glutathione and superoxide dismutase, decreases maloaldehyde content [182–184] Stimulates AMPK-FOXO3 [185] Downregulates Rictor [190] Stimulation of TLR-4 pathway [192] Blocking of IκB kinase activity [193, 194] Activation of MAPKs and AP-1 pathway [194, 195] Increases Apaf-1 [196, 197] Decreases the expression of extracellular signal-regulated kinase 1/2 and p38 [198] Inhibition of accumulation of hypoxia-inducible factor-1α and VEGF expression [204] Blockage of NF-κB pathway [216] Cell survival prolongation: reduces ROS formation, leads to PARP cleavage, and induces autophagy [217] Accumulation of ceramide and autophagy [232] Inhibition of APE/Ref-1, with decreasing of Ap-1/JunD, MMP-1, and iNOS, α-MSH [227, 230, 231] Reduction of AMP-activated protein kinase, COX-2, vasodilator-stimulated phosphoprotein, and VEGF [211, 233] Increasing the expression of thrombospondin-1 with decreasing of the VEGF-sensitive hypoxia inducible factor-1α [42] Inhibition of lipopolysaccharide-induced epithelian-mesenchymal transition of IL-8 [235] Inhibition of NO production in VEGF-stimulated endothelial cells and of COX-2 induction [236]
Salicylic acid	Intracellular depletion of gluthatione [237]
Tannic acid	Downregulation of UVB-induced IL-18 [261]

AMP adenosine monophosphate, AMPK-FOXO3 5′AMP-activated protein kinase/forkhead box protein O3, AP-1 activator protein-1, AP-1/JunD activator protein-1/JunD protein, Apaf-1 apoptotic protease-activating factor-1, APE/Ref-1 apurinic/apyrimidinic endonuclease/redox effector factor-1; ATP adenosine triphosphate, CD8+ T-cell cytotoxic T cell CD8 positive, COX-2 cyclooxygenase-2, COX-2 NF-κB cyclooxygenase-2 expression through nuclear factor-kappa B, DNA deoxyribonucleic acid, dUTP 2′-deoxyuridine 5′-triphosphate, G1 Gap 1, ICAM-1 intercellular adhesion molecule-1, IFN-γ interferon gamma, IGF-1 insulin growth factor-1, IL-1β interleukin-1 beta, IL-6 interleukin-6, IL-8 interleukin-8, IL-18 interleukin-18, iNOS inducible nitric oxide synthase, Ki-67 protein Ki-67, MAPK mitogen-activated protein kinase, MCP-1 monocyte chemoattractant protein-1, MMP-1 metalloproteinase-1, α-MSH alpha-melanocyte-stimulating hormone, NF-κβ nuclear factor–kappa B, NO nitric oxide, Nrf2 nuclear factor-like 2, p-4EBP1 phosphorylation of eukaryotic translation initiation factor 4E binding protein-1, p38 protein p38, PARP poly ADP (adenosine diphosphate) ribose polymerase, PCNA proliferation cell nuclear antigen, PGE-2 prostaglandin E2, ROS reactive oxygen species, TLR-4 toll-like receptor-4, TNF-α tumor necrosis factor alpha, TUNEL terminal dUTP nick end labeling, UVA ultraviolet A, UVB ultraviolet B, VEGF vascular endothelial growth factor